Vaginal vault smear cytology in detection of recurrence after hysterectomy for early cervical cancer.

OBJECTIVE: To determine the role of vaginal vault cytology as a surveillance tool for the detection of recurrence in patients with early stage cervical cancer treated with hysterectomy without adjuvant therapy. METHODS: A retrospective cohort study was conducted of all women with cervical cancer treated with a hysterectomy from January 2000 to July 2016 at the Royal Brisbane & Women's Hospital, Australia. Women included were diagnosed with the equivalent of International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1A1 to 1B3 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, received either simple or radical hysterectomy with or without pelvic lymph node dissection, and did not receive adjuvant therapy. Age, stage, histology, surgical procedure, and details of individual surveillance regimens including examination findings and indications and results for all vault cytology tests performed in the first 5 years following surgical management were collected. RESULTS: A total of 155 women met the inclusion criteria. Most cases were FIGO 2018 stage 1B1 (61.9%) and squamous cell carcinoma (64.5%). Included women underwent a median of 80 months of surveillance (range 25-200, IQR 64-108). In the first 5 years of surveillance, there were a total of 1001 vault cytology smears performed, with a median of 6 smears (IQR 5-9) per woman. A total of 19 smears were abnormal (1.9%). Of the cohort of 155 women, 19 (12.3%) had an abnormality detected; 1 (0.65%) had a high-grade intraepithelial abnormality and 2 (1.3%) had recurrences detected on cytology; however, a lesion was also seen and biopsied in all three women. A total of 16 of 1001 smears (1.6%) had low-grade abnormalities detected, all of which resolved with clinical observation only. All were alive and well at last review. There were in total 6 (3.9%) recurrences, 2 (33%) of which had abnormal cytology as above, and all of which had a lesion to biopsy and/or abnormal medical imaging. CONCLUSIONS: The routine use of vaginal vault cytology in surveillance following hysterectomy for early stage cervical cancer did not appear to alter the detection of recurrent malignancy.

Cervical Cancer Prevention in Low- and Middle-Income Countries.

Cervical cancer is one of the commonest cancers afflicting women in low and middle income countries, however, both primary prevention with human papillomavirus vaccination, and secondary prevention with screening programs and treatment of preinvasive disease are possible. A coordinated approach to eliminating cervical cancer, as has been called for by the World Health Organization, requires a complex series of steps at all levels of a health system. This article outlines the current state of cervical cancer prevention in low and middle income countries, the innovations being employed to improve outcomes, and consideration of the next steps needed as we move towards global elimination.

A systematic review and meta-analysis of sarcopenia as a prognostic factor in gynecological malignancy.

INTRODUCTION: Sarcopenia is a condition described as the progressive generalized loss of muscle mass and strength. While sarcopenia has been linked with poorer outcomes following a variety of malignancies, its relationship with all gynecological cancer clinical outcomes has, to date, not been evaluated. This review interrogates the concept of sarcopenia as a prognostic tool for oncological outcomes and adverse effects of treatments in all primary gynecological malignancies. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines, searching PubMed, Embase, and CINAHL without date or language restriction for studies reporting on sarcopenia and gynecological malignancies. Random effects meta-analysis models were used to determine the effects of sarcopenia on progression-free survival, overall survival, and treatment-related adverse events. RESULTS: Data were analyzed from 13 studies, including 2446 patients (range 60-323) with ovarian cancer (n=1381), endometrial cancer (n=354), or cervical cancer (n=481). Sarcopenia was associated with lower progression-free survival (HR 1.69, 95% CI 1.03 to 2.76), overall survival (HR 1.33, 95% CI 1.08 to 1.64), and no increase in adverse events (HR 1.28, 95% CI 0.69 to 2.40). The risk of bias of the studies was mostly rated unclear, and Begg's and Egger's test revealed a potential publication bias for progression-free survival and overall survval, although the HRs remained significant when adjusting for it. CONCLUSION: Sarcopenia is associated with worse progression-free survival and overall survival in gynecological oncology malignancies. Further research is warranted to validate these findings in larger and prospective samples using standardized methodology and to examine if an intervention could reverse its effect in gynecological oncology trials.

A before and after study of the impact on obstetric and perinatal outcomes following the introduction of an educational package of fetal heart rate monitoring education coupled with umbilical artery lactate sampling in a low resource setting labor ward in South Africa.

INTRODUCTION: Rates of cesarean section (CS) are increasing and abnormal fetal heart rate tracing and concern about consequent acidosis remain one of the most common indications for primary CS. Umbilical artery (UA) lactate sampling provides clinicians with point of care feedback on CTG interpretation and intrapartum care and may result in altered future practice. MATERIALS AND METHODS: From 3rd March - 12th November 2014 we undertook a before and after study in Pretoria, South Africa, to determine the impact of introducing a clinical package of fetal heart rate monitoring education and prompt feedback with UA cord lactate sampling, using a hand-held meter, on maternal and perinatal outcomes. RESULTS: Nine hundred thirty-six consecutive samples were analyzed (pre n = 374 and post n = 562). There was no difference in mean lactate (4.6 mmol/L [95%CI 4.4-4.8] compared with 4.9 mmol/L [95%CI 4.7-5.1], p = 0.089). Suspected fetal compromise was reduced in the post-intervention period: 30·2% vs 22·1%, aOR 0·71, 95% CI 0·52-0·96, p = 0·027. Cesarean section rates were significantly reduced in the univariate analysis: pre- 40·3% vs post-intervention 31·6% (p = 0·007). This reduction remained significant when adjusted for previous cesarean section, primiparity, maternal HIV infection and preterm birth (aOR 0·72, 95%CI 0·54-0·98, p = 0·035). Neonatal outcomes did not differ between the two groups. CONCLUSION: The introduction of a clinical practice package of fetal heart rate monitoring education combined with routine UA cord lactate sampling has the potential to reduce the cesarean section rate without increasing adverse neonatal outcomes in a low-resource setting.

Applying the international classification of diseases to perinatal mortality data, South Africa.

OBJECTIVE: To examine the feasibility of applying the International Classification of Diseases-perinatal mortality (ICD-PM) coding to an existing data set in the classification of perinatal deaths. METHODS: One author, a researcher with a non-clinical public health background, applied the ICD-PM coding system to South Africa's national perinatal mortality audit system, the Perinatal Problem Identification Program. The database for this study included all perinatal deaths (n = 26 810), defined as either stillbirths (of birth weight > 1000 g and after 28 weeks of gestation) or early neonatal deaths (age 0-7 days), that occurred between 1 October 2013 and 31 December 2016. A clinical obstetrician verified the coding. FINDINGS: The South African classification system does not include the timing of death; however, under the ICD-PM system, deaths could be classified as antepartum (n = 15 619; 58.2%), intrapartum (n = 3725; 14.0%) or neonatal (n = 7466; 27.8%). Further, the South African classification system linked a maternal condition to only 40.3% (10 802/26 810) of all perinatal deaths; this proportion increased to 68.9% (18 467/26 810) under the ICD-PM system. CONCLUSION: The main benefit of using the clinically relevant and user-friendly ICD-PM system was an enhanced understanding of the data, in terms of both timing of death and maternal conditions. We have also demonstrated that it is feasible to convert an existing perinatal mortality classification system to one which is globally comparable and can inform policy-makers internationally.

Stillbirths: progress and unfinished business.

This first paper of the Lancet Series on ending preventable stillbirths reviews progress in essential areas, identified in the 2011 call to action for stillbirth prevention, to inform the integrated post-2015 agenda for maternal and newborn health. Worldwide attention to babies who die in stillbirth is rapidly increasing, from integration within the new Global Strategy for Women's, Children's and Adolescents' Health, to country policies inspired by the Every Newborn Action Plan. Supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging. Prenatal health is a crucial biological foundation to life-long health. A key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health. Still, specific actions for stillbirths are needed for advocacy, policy formulation, monitoring, and research, including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival. Strong leadership is needed worldwide and in countries. Institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies.

Attitudes towards the implementation of universal umbilical artery lactate analysis in a South African district hospital.

BACKGROUND: Of the 5.54 million stillbirths and neonatal deaths occurring globally each year, a significant amount of these occur in the setting of inadequate intrapartum care. The introduction of universal umbilical artery lactate (UA) measurements in this setting may improve outcomes by providing an objective measurement of quality of care and stimulating case reflection, audit, and practice change. It is important that consideration is given to the barriers and facilitators to implementing this tool outside of a research setting. METHODS: During the period 16/11/2014 -13/01/2015, we conducted a training course in cardiotocograph (CTG) interpretation, fetal physiology, and the sampling and analysing of UA lactate, with a pre and post questionnaire aimed at assessing the barriers and facilitators to the introduction of universal UA lactate in a district hospital in the Eastern Cape, South Africa. RESULTS: Thirty-five pre-training questionnaires available (overall response rate 95 %) and 22 post training questionnaires (response rate 63 %) were available for analysis. Prior to training, the majority gave positive responses (strongly agree or agree) that measuring UA lactate assists neonatal care, is protective for staff medicolegally, and improves opportunities for audit and teaching of maternity practice (n = 33, 30, 32; 94.4 %, 85.7 %, 91.4 % respectively). Respondents remained positive about the benefits post training. An increased workload on medical or midwifery staff was less likely to be seen as barrier following training (71 vs. 38.9 % positive response, p = 0.038). A higher rate of respondents felt that expense and lack of equipment were likely to be barriers after completing training, although this wasn't significant. There was a trend towards lack of time and expertise being less likely to be seen as barriers post training. CONCLUSION: The majority of participants providing intrapartum care in this setting are positive about the role of universal UA lactate analysis and the potential benefits it provides. Training aids in overcoming some of the perceived barriers to implementation of universal UA lactate analysis.

Quality-of-care audits and perinatal mortality in South Africa.

PROBLEM: Suboptimal care contributes to perinatal mortality rates. Quality-of-care audits can be used to identify and change suboptimal care, but it is not known if such audits have reduced perinatal mortality in South Africa. APPROACH: We investigated perinatal mortality trends in health facilities that had completed at least five years of quality-of-care audits. In a subset of facilities that began audits from 2006, we analysed modifiable factors that may have contributed to perinatal deaths. LOCAL SETTING: Since the 1990s, the perinatal problem identification programme has performed quality-of-care audits in South Africa to record perinatal deaths, identify modifiable factors and motivate change. RELEVANT CHANGES: Five years of continuous audits were available for 163 facilities. Perinatal mortality rates decreased in 48 facilities (29%) and increased in 52 (32%). Among the subset of facilities that began audits in 2006, there was a decrease in perinatal mortality of 30% (16/54) but an increase in 35% (19/54). Facilities with increasing perinatal mortality were more likely to identify the following contributing factors: patient delay in seeking help when a baby was ill (odds ratio, OR: 4.67; 95% confidence interval, CI: 1.99-10.97); lack of use of antenatal steroids (OR: 9.57; 95% CI: 2.97-30.81); lack of nursing personnel (OR: 2.67; 95% CI: 1.34-5.33); fetal distress not detected antepartum when the fetus is monitored (OR: 2.92; 95% CI: 1.47-5.8) and poor progress in labour with incorrect interpretation of the partogram (OR: 2.77; 95% CI: 1.43-5.34). LESSONS LEARNT: Quality-of-care audits were not shown to improve perinatal mortality in this study.

Causes of perinatal mortality and associated maternal complications in a South African province: challenges in predicting poor outcomes.

BACKGROUND: Reviews of perinatal deaths are mostly facility based. Given the number of women who, globally, deliver outside of facilities, this data may be biased against total population data. We aimed to analyse population based perinatal mortality data from a LMIC setting (Mpumalanga, South Africa) to determine the causes of perinatal death and the rate of maternal complications in the setting of a perinatal death. METHODS: A secondary analysis of the South African Perinatal Problems Identification Program (PPIP) database for the Province of Mpumalanga was undertaken for the period October 2013 to January 2014, inclusive. Data on each individual late perinatal death was reviewed. We examined the frequencies of maternal and fetal or neonatal characteristics in late fetal deaths and analysed the relationships between maternal condition and fetal and/or neonatal outcomes. IBM SPSS Statistics 22.0 was used for data analysis. RESULTS: There were 23503 births and 687 late perinatal deaths (stillbirths of ≥ 1000gr or ≥ 28 weeks gestation and early neonatal deaths up to day 7 of neonatal life) in the study period. The rate of maternal complication in macerated stillbirths, fresh stillbirths and early neonatal deaths was 50.4%, 50.7% and 25.8% respectively. Mothers in the other late perinatal deaths were healthy. Maternal hypertension and obstetric haemorrhage were more likely in stillbirths (p = <0.01 for both conditions), whereas ENNDs were more likely to have a healthy mother (p < 0.01). The main causes of neonatal death were related to immaturity (48.7%) and hypoxia (40.6%). 173 (25.2%) of all late perinatal deaths had a birth weight less than the 10(th) centile for gestational age. CONCLUSION: A significant proportion of women have no recognisable obstetric or medical condition at the time of a late perinatal death; we may be limited in our ability to predict poor perinatal outcome if emphasis is put on detecting maternal complications prior to a perinatal death. Intrapartum care and hypertensive disease remain high priority areas for addressing perinatal mortality. Consideration needs to be given to novel ways of detecting growth restriction in a LMIC setting.

The global burden of cervical cancer requiring surgery: database estimates.

BACKGROUND: Scaling up surgical services for cervical cancer in low and middle income countries requires quantification of the need for those services. The aim of this study was to estimate the global burden of cervical cancer for which access to surgery is required. METHODS: This was a retrospective analysis of publicly available data. Cervical cancer incidence was extracted for each country from the World Health Organization, International Agency for Research, Global Cancer Observatory. The proportion of cases requiring surgery was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The need for cervical cancer surgery was tested against development indicators. RESULTS: Data were available for 175 countries, representing 2.9 billion females aged 15 and over. There were approximately 566,911 women diagnosed with cervical cancer (95% CI 565,462-568,360). An estimated 56.9% of these women (322,686) would require surgery for diagnosis, treatment or palliation (95% CI 321,955 - 323,417). Cervical cancers for which surgery is required represent less than 1% of cancers in high income countries, and nearly 10% of cancers in low income countries. CONCLUSIONS: At least 300,000 cervical cancer cases worldwide require access to surgical services annually. Gathering data on available cervical cancer surgery services in LMIC are a critical next step.

Preventing Cervical Cancer Globally: Are We Making Progress?

An unacceptable number of women continue to die from cervical cancer around the world each year. Despite established primary and secondary prevention measures, and a natural history of disease which provides a long latent phase in which to intervene, there are still more than 500,000 women diagnosed with cervical cancer globally each year, and 300,000 related deaths. Approximately 90% of these cervical cancer cases and deaths occur in low- and middle-income countries (LMIC). The World Health Organization (WHO) recently launched a Global Strategy to Accelerate the Elimination of Cervical Cancer that outlines 3 key steps: (i) vaccination against human papillomavirus (HPV); (ii) cervical screening; and (iii) treatment of precancerous lesions and management of invasive cancer. Successful implementation of all 3 steps could reduce more than 40% of new cervical cancer cases and 5 million related deaths by 2050. However, this initiative requires high level commitment to HPV immunization programs, innovative approaches to screening, and strengthening of health systems to provide treatment for both precancerous lesions as well as invasive cervical cancer.

Accuracy of Smartphone Images of the Cervix After Acetic Acid Application for Diagnosing Cervical Intraepithelial Neoplasia Grade 2 or Greater in Women With Positive Cervical Screening: A Systematic Review and Meta-Analysis.

PURPOSE: Smartphones are used in cervical screening for visual inspection after acetic acid or Lugol's iodine (VIA/VILI) application to capture and share images to improve the sensitivity and interobserver variability of VIA/VILI. We undertook a systematic review and meta-analysis assessing the diagnostic accuracy of smartphone images of the cervix at the time of VIA/VILI (termed S-VIA) in the detection of precancerous lesions in women undergoing cervical screening. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies from January 1, 2010, to June 30, 2020, were assessed. MEDLINE/PubMed, Embase, CINAHL, Cochrane, and LILACS were searched. Cohort and cross-sectional studies were considered. S-VIA was compared with the reference standard of histopathology. We excluded studies where additional technology was added to the smartphone including artificial intelligence, enhanced visual assessment, and other algorithms to automatically diagnose precancerous lesions. The primary outcome was the accuracy of S-VIA for the diagnosis of cervical intraepithelial neoplasia grade 2 or greater (CIN 2+). Data were extracted, and we plotted the sensitivity, specificity, negative predictive value, and positive predictive value of S-VIA using forest plots. This study was prospectively registered with The International Prospective Register of Systematic Reviews:CRD42020204024. RESULTS: Six thousand three studies were screened, 71 full texts assessed, and eight studies met criteria for inclusion, with six included in the final meta-analysis. The sensitivity of S-VIA for the diagnosis of CIN 2+ was 74.56% (95% CI, 70.16 to 78.95; I2 61.30%), specificity was 61.75% (95% CI, 56.35 to 67.15; I2 95.00%), negative predictive value was 93.71% (95% CI, 92.81 to 94.61; I2 0%), and positive predictive value was 26.97% (95% CI, 24.13 to 29.81; I2 61.3%). CONCLUSION: Our results suggest that S-VIA has accuracy in the detection of CIN 2+ and may provide additional support to health care providers delivering care in low-resource settings.

Pretreatment With Mifepristone Compared With Misoprostol Alone for Delivery After Fetal Death Between 14 and 28 Weeks of Gestation: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of pretreatment with mifepristone before misoprostol, compared with misoprostol alone, for termination of pregnancy after a fetal death in the second trimester. METHODS: This prospective, double blind, placebo-controlled trial randomized women requiring a termination of pregnancy after fetal death between 14 and 28 weeks of gestation to placebo or 200 mg mifepristone orally 24-48 hours before the termination of pregnancy with misoprostol (400 micrograms every 6 hours vaginally for women at 24 weeks of gestation or less, and 200 micrograms every 4 hours vaginally for women at 24 weeks of gestation or more). Based on a median labor with misoprostol alone in the second trimester of 13 hours, a sample size of 116 women per group was planned to compare the primary outcome of time from administration of misoprostol to delivery. The trial was ceased after 66 women were enrolled secondary to prolonged time to achieve recruitment. RESULTS: From April 2013 to November 2016, 66 women were randomized (34 to placebo and 32 to mifepristone). There were no differences in the characteristics between the two groups. The median time for the primary outcome of administration of misoprostol to delivery in the placebo group was 10.5 hours, compared with 6.8 hours in the treatment group (hazard ratio 2.41 95% CI 1.39-4.17, P=.002). Women in the placebo group required more doses of misoprostol (3.4 vs 2.1, P=.002) and more misoprostol overall (1,181.8 micrograms, vs 767.7 micrograms, P=.003). There was no difference in maternal complications between the two groups. Women in the mifepristone group reported improved perception of the procedure. CONCLUSION: The sequential use of mifepristone and misoprostol for the termination of pregnancy after fetal deaths between 14 and 28 weeks of gestation reduces the time to delivery, compared with the use of misoprostol alone, with no worsening of maternal complications. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000884808.

Morbidity after surgical management of cervical cancer in low and middle income countries: A systematic review and meta-analysis.

OBJECTIVE: To investigate morbidity for patients after the primary surgical management of cervical cancer in low and middle-income countries (LMIC). METHODS: The Pubmed, Cochrane, the Cochrane Central Register of Controlled Trials, Embase, LILACS and CINAHL were searched for published studies from 1st Jan 2000 to 30th June 2017 reporting outcomes of surgical management of cervical cancer in LMIC. Random-effects meta-analytical models were used to calculate pooled estimates of surgical complications including blood transfusions, ureteric, bladder, bowel, vascular and nerve injury, fistulae and thromboembolic events. Secondary outcomes included five-year progression free (PFS) and overall survival (OS). FINDINGS: Data were available for 46 studies, including 10,847 patients from 11 middle income countries. Pooled estimates were: blood transfusion 29% (95%CI 0.19-0.41, P = 0.00, I2 = 97.81), nerve injury 1% (95%CI 0.00-0.03, I2 77.80, P = 0.00), bowel injury, 0.5% (95%CI 0.01-0.01, I2 = 0.00, P = 0.77), bladder injury 1% (95%CI 0.01-0.02, P = 0.10, I2 = 32.2), ureteric injury 1% (95%CI 0.01-0.01, I2 0.00, P = 0.64), vascular injury 2% (95% CI 0.01-0.03, I2 60.22, P = 0.00), fistula 2% (95%CI 0.01-0.03, I2 = 77.32, P = 0.00,), pulmonary embolism 0.4% (95%CI 0.00-0.01, I2 26.69, P = 0.25), and infection 8% (95%CI 0.04-0.12, I2 95.72, P = 0.00). 5-year PFS was 83% for laparotomy, 84% for laparoscopy and OS was 85% for laparotomy cases and 80% for laparoscopy. CONCLUSION: This is the first systematic review and meta-analysis of surgical morbidity in cervical cancer in LMIC, which highlights the limitations of the current data and provides a benchmark for future health services research and policy implementation.

Impact of maternal HIV on umbilical cord lactate measurement at delivery in a South African labor ward.

OBJECTIVE: To assess umbilical artery lactate levels and perinatal outcomes among women with and without HIV infection. METHODS: The present prospective cohort study recruited women planning to undergo vaginal delivery at Kalafong Hospital, South Africa, between March 3 and November 12, 2014. Umbilical artery lactate levels were measured and perinatal outcome data were recorded. Outcome analyses were stratified by maternal HIV status, and a subgroup analysis was performed where women with a CD4 count below 350 × 106 cells/L were compared with women without HIV. RESULTS: In total, 936 women with singleton fetuses were enrolled. Maternal HIV status was available for 897 (95.8%) participants, of whom 202 (21.6%) had HIV infections. Overall, 186 (92.1%) women with HIV infections received prophylaxis or treatment. There was no difference between participants with and without HIV infections in the preterm delivery rate (P=0.770), mode of delivery (P=0.354), neonatal resuscitation rate (P=0.717), 1- or 5-minute Apgar scores below 7 (P=0.353), or the rate of having an umbilical artery lactate level above 5.45 mmol/L (P=0.301). Similarly, there were no differences in outcomes in the subgroup analysis of women with a CD4 count below 350 × 106 cells/L. CONCLUSION: Umbilical artery lactate levels and perinatal outcomes were found to be comparable between patients with and without HIV infections in a South African setting.

Implementation of effective practices in health facilities: a systematic review of cluster randomised trials.

BACKGROUND: The capacity for health systems to support the translation of research in to clinical practice may be limited. The cluster randomised controlled trial (cluster RCT) design is often employed in evaluating the effectiveness of implementation of evidence-based practices. We aimed to systematically review available evidence to identify and evaluate the components in the implementation process at the facility level using cluster RCT designs. METHODS: All cluster RCTs where the healthcare facility was the unit of randomisation, published or written from 1990 to 2014, were assessed. Included studies were analysed for the components of implementation interventions employed in each. Through iterative mapping and analysis, we synthesised a master list of components used and summarised the effects of different combinations of interventions on practices. RESULTS: Forty-six studies met the inclusion criteria and covered the specialty groups of obstetrics and gynaecology (n=9), paediatrics and neonatology (n=4), intensive care (n=4), internal medicine (n=20), and anaesthetics and surgery (n=3). Six studies included interventions that were delivered across specialties. Nine components of multifaceted implementation interventions were identified: leadership, barrier identification, tailoring to the context, patient involvement, communication, education, supportive supervision, provision of resources, and audit and feedback. The four main components that were most commonly used were education (n=42, 91%), audit and feedback (n=26, 57%), provision of resources (n=23, 50%) and leadership (n=21, 46%). CONCLUSIONS: Future implementation research should focus on better reporting of multifaceted approaches, incorporating sets of components that facilitate the translation of research into practice, and should employ rigorous monitoring and evaluation.